Elucidation of a brain network underlying social memory – WhoRU

While the ability to form and recall memories is essential for survival, it is also key to forming relationships with others and defines our sense of self. The hippocampus has long been recognized as a fundamental structure for learning and memory formation. Many lesion studies of human patients over the course of the last 50 years have revealed that the hippocampus is required for the formation of long term episodic memories. The focus of this project is on social memory, a hippocampal-dependent process of fundamental importance. The inability to properly recognize family and acquaintances is frequently an early symptom of several psychiatric disorders and neurological diseases, and a strong predictor of patient outcome. Hippocampal area CA2 has recently been found to be essential for social memory formation. Interestingly, this area also shows marked vulnerability in numerous psychiatric and neurodegenerative diseases. The goal of this proposal is to understand the brain circuitry and network mechanisms underlying social memory formation.

Social recognition memory is the ability to differentiate between an unknown and familiar conspecific. In humans and rodents, normal hippocampal function is required for social recognition memory. The inability to recall social interactions is one of the more prominent characteristics of patients with hippocampal lesions. Much has been learned about spatial encoding by ensembles of cells and network activity of the hippocampus, and interestingly there is compelling evidence in human studies indicating that social relations are mapped within the hippocampus. However, how social information is processed and encoded by the hippocampus is not understood.

The first aim of this project is to determine what differentiates social information from contextual information in the hippocampal circuit. Recent findings have revealed a surprising role played by chemosignals in human social cognition, a process that is disrupted in autism spectrum disorder. In rodents, olfaction plays a crucial role in social recognition memory, as ablation of the olfactory bulbs or vomeronasal organ prevents social recognition memory. We hypothesize area CA2 is particularly tuned to be sensitive to chemosignals associated with social context, as it receives several inputs from brain regions that are strongly activated by olfactory system and hormonal signals. Thus, in this aim, we will examine the neural circuits activated by social olfactory input and determine how they influence hippocampal area CA2.

The second aim of this project is to examine if area CA2 acts on the hippocampal and septal network to enable encoding of social memories. There is abundant recent evidence that area CA2 neurons project and act very widely on the hippocampal and septal network. With this, it has recently been shown that ensembles of cells in ventral CA1 are active during social learning, and selective re-activation of this sparse population is able to alter performance in a social memory task. We hypothesize that dorsal CA2 pyramidal neurons are acting on ventral CA1 pyramidal neurons and the septum during social episodes, allowing the encoding of social information. Thus, in this aim, we will examine how dorsal CA2 activity acts on ventral CA1 pyramidal neurons and the medial septum.

Hippocampal area CA2 has gone virtually un-studied for the last seventy years. In this project three teams with very complementary sets of expertise will apply several cutting-edge techniques including optogenetics, behavioral testing, neuronal circuitry mapping and in vivo recording to better understand social memory formation. Our results will provide a link and mechanism to understanding how social information is processed and provides the foundation for finding new diagnosis and treatments for psychiatric disease.